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Major Bennett Marco, Sergeant Raymond Shaw, and the rest of their infantry platoon are captured by an elite Soviet commando unit during the Korean War in 1952. They are taken to Manchuria, and brainwashed into believing Shaw saved their lives in combat – for which Shaw is subsequently awarded the Medal of Honor.

Years after the war, Marco, now back in the United States working as an intelligence officer, begins suffering a recurring nightmare. In the dreams that Major Marco was experiencing, the platoon were all together surrounded by what appeared to be sweet little old ladies, a part of their brainwashing. The platoon was seated together and one of the ladies tells Sergeant Shaw to murder two of his comrades from his platoon. The backdrop with the old ladies changes back and forth between them and Chinese and Soviet intelligence officials. When Marco learns that another soldier from the platoon has been suffering the same nightmare, he investigates why this is happening.

Major Marco looks up Sergeant Raymond Shaw and discovers that Raymond's new manservant is someone that he recognizes from Korea. They start fighting in Raymond's house and both get bloodied significantly. Marco is arrested, and when Shaw sees that it's his old Major, they rekindle their relationship. Both find love interests; for Marco, it's Rose Cheyney, and for Raymond, it's Jocelyn Jordan. Jocelyn Jordan is the daughter of Senator Thomas Jordan, who is a neighbor of Raymond Shaw's. Senator Jordan and Raymond's mother don't like each other, but Raymond continues to see Jocelyn.

It is revealed that the Communists have been using Shaw as a sleeper agent who, activated by a posthypnotic trigger, immediately forgets the assignments he carries out and therefore can never betray himself either purposely or inadvertently. In Shaw's case, the suggestion that he play solitaire is the trigger. Seeing the "Queen of Diamonds" playing card transforms him into an assassin who will kill anyone at whom he is directed. Shaw’s KGB handler is his domineering mother, Eleanor. Married to McCarthy-esque Senator Johnny Iselin, Eleanor has convinced the Communist powers to help her install her husband as president and allow them to control the American government through him.

By observing Shaw, Marco discovers the trigger shortly before the national convention of Iselin's political party. He uses the Queen of Diamonds card to draw out Eleanor's plan: after she obtains the vice presidential nomination for Iselin, Shaw is to shoot the presidential candidate so that Iselin can succeed him. Blaming the killing on the Communists will enable Iselin to assume dictatorial powers. Marco reprograms Shaw, although it is unclear until the final pages whether this is successful. At the convention, Shaw instead shoots and kills his mother and Senator Iselin. Marco is the first person to reach Shaw's sniper nest, getting there just before Shaw turns the gun on himself.[2]

In 1998, software developer C. J. Silverio noted that several long passages of the novel seemed to be adapted from Robert Graves' 1934 novel I, Claudius. Forensic linguist John Olsson judged that "There can be no disputing that Richard Condon plagiarized from Robert Graves." Olsson went on to state that "As plagiarists go, Condon is quite creative, he does not confine himself to one source and is prepared to throw other ingredients into the pot."[3]Jonathan Lethem, in his influential essay The Ecstasy of Influence: A Plagiarism, has identified The Manchurian Candidate as one of a number of "cherished texts that become troubling to their admirers after the discovery of their 'plagiarized' elements," which make it "apparent that appropriation, mimicry, quotation, allusion, and sublimated collaboration consist of a kind of sine qua non of the creative act, cutting across all forms and genres in the realm of cultural production."[4]

The Manchurian Candidate (2004) was directed by Jonathan Demme, and starred Liev Schreiber as Shaw, Denzel Washington as Marco, and Meryl Streep as Eleanor. It was generally well received by critics, and moderately successful at the box office. The film updated the conflict (and brainwashing) to the Persian Gulf War in 1991, emphasized the science fiction aspects of the story by setting the action in a dystopian near-future (implied to be 2008), had a U.S. corporation (called "Manchurian Global") as the perpetrator of the brainwashing and conspiracy instead of foreign Communist groups, and dropped the Johnny Iselin character in favor of making both Shaw and his mother elected politicians.

Both adaptations discard several elements of the book. The book spends more time describing the brainwashers and the facility in Manchuria where the Americans were held. The head of the project grants Raymond a "gift"; after his brainwashing, he becomes quite sexually active, in contrast to his reserved nature beforehand where he had not even kissed his love interest, Jocelyn Jordan.

In the novel, Mrs. Iselin and her son travel abroad, where she uses him to kill various political figures and possibly Jocelyn Jordan's first husband. Rosie, Marco's love interest, is the ex-fiancee of one of his associates handling the Shaw case for Army Intelligence, making things between the couple tense. The movie adaptations also all but omit the novel's portrayal of incest between Raymond and his mother, only hinting at it with a mouth-to-mouth kiss.

As a child, Mrs. Iselin was sexually abused by her father, but fell in love with him and idolized him after his early death. Towards the end of the book, as Raymond is hypnotized by the Queen of Diamonds, he reminds her of her father and they sleep together.

The 1962 version does not state outright the political affiliation of Senators Iselin and Jordan (implied to be Republicans), although in the 2004 film the equivalent characters are Democrats. According to David Willis McCullough, Senator Iselin is modelled on Republican senator Joseph McCarthy and, according to Condon, Shaw's mother is based on McCarthy's counsel Roy Cohn.[6]